Method and device for the determination of platelet function under flow conditions
The invention lies in the area of platelet function diagnostics and relates to a method for the determination of platelet function under flow conditions as well as a device for the implementation of this method. The method is particularly suitable for the determination of the effect of clopidogrel and of other P2Y(12) antagonists with antithrombotic activity as well as the determination of P2Y(1) antagonists with antithrombotic activity.
1 . A method for the determination of platelet function in a whole blood sample, the method comprising the following steps:
a) passing the blood through a capillary and then through an opening of a partition member; and
b) measuring the time that is required for the formation of a thrombus at the opening of the partition member up to closure of the opening;
wherein
the partition member comprises:
i) an activator of purinergic receptors and
ii) an activator of intracellular adenylate cyclases.
2 . The method as claimed in claim 1 , wherein the partition member comprises in addition calcium ions.
3 . The method as claimed in claim 1 wherein the partition member used comprises an activator of purinergic receptors from the group adenosine-5′-diphosphate, 2-methylthioadenosine-5′-diphosphate, and their derivatives.
4 . The method as claimed in claim 1 , wherein the partition member comprises an activator of intracellular adenylate cyclases from the group prostaglandin E1, forskolin and their derivatives, prostaglandin I2 and its stable derivatives, illoprost, and cicaprost.
5 . The method as claimed in claim 1 , wherein the whole blood sample is anticoagulated with a direct thrombin inhibitor.
6 . The method as claimed in claim 1 , wherein the whole blood sample is anticoagulated with a direct Factor Xa inhibitor.
7 . The method as claimed in claim 2 , wherein the whole blood sample is anticoagulated with citrate.
8 . The method as claimed in claim 1 wherein the method determines the antithrombotic effect of a P2Y(12) antagonist.
9 . The method as claimed in claim 8 wherein the P2Y(12) antagonist is selected from clopidogrel, ticlopidine, prasugrel, AR-C67085MX, cangrelor, C1330-7, MRS 2395, and 2-methylthioadenosine-5′-monophosphate.
10 . The method as claimed in claim 1 wherein the method determines the antithrombotic effect of a P2Y(1) antagonist.
11 . The method as claimed in claim 10 wherein the P2Y(1) antagonist is selected from MRS 2179, MRS 2279, MRS 2500, A2P5P, A3P5P, and A3P5PS.
12 . A device for the determination of platelet function in a whole blood sample wherein the device comprises the following elements:
a) a reservoir for holding the sample;
b) a capillary through which the blood is passed from the reservoir into a measurement chamber;
c) a measurement chamber that is divided into two compartments by a partition member, wherein the first compartment receives the blood from the capillary;
d) a partition member that divides the measurement chamber into two compartments and has an opening through which the blood can flow from the first compartment into the second compartment;
wherein
the partition member comprises
i) an activator of purinergic receptors and
ii) an activator of intracellular adenylate cyclases.
13 . The device as claimed in claim 12 , wherein the partition member also comprises calcium ions.
14 . A method for the determination of platelet function in a whole blood sample, comprising passing the blood sample through the device as claimed in claim 12 .
15 . The method as claimed in claim 14 wherein the method determines the antithrombotic effect of a P2Y(12) antagonist.
16 . The method as claimed in claim 14 wherein the method determines the antithrombotic effect of a P2Y(1) antagonist.